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Article ; Online: REPLY.

Otero Sanchez, Lukas / Karakike, Eleni / Moreno, Christophe / Trépo, Eric / Gustot, Thierry

2021 Volume 74, Issue 5, Page(s) 2927–2928

Language	English
Publishing date	2021-08-31
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.32057
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Zs.A 1660: Show issues

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Article ; Online: Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis.

Karakike, Eleni / Giamarellos-Bourboulis, Evangelos J

Frontiers in immunology

2019 Volume 10, Page(s) 55

Abstract: Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of ... ...

Abstract	Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of genes encoding for perforin or excretory granules of natural killer (NK) cells of CD8-lymphocytes. sHLH is also known as macrophage activation syndrome (MAS). Macrophage activation syndrome (MAS) in adults is poorly studied. Main features are fever, hepatosplenomegaly, hepatobiliary dysfunction (HBD), coagulopathy, cytopenia of two to three cell lineages, increased triglycerides and hemophagocytosis in the bone marrow. sHLH/MAS complicates hematologic malignancies, autoimmune disorders and infections mainly of viral origin. Pathogenesis is poorly understood and it is associated with increased activation of macrophages and NK cells. An autocrine loop of interleukin (IL)-1β over-secretion leads to cytokine storm of IL-6, IL-18, ferritin, and interferon-gamma; soluble CD163 is highly increased from macrophages. The true incidence of sHLH/MAS among patients with sepsis has only been studied in the cohort of the Hellenic Sepsis Study Group. Patients meeting the Sepsis-3 criteria and who had positive HSscore or co-presence of HBD and disseminated intravascular coagulation (DIC) were classified as patients with macrophage activation-like syndrome (MALS). The frequency of MALS ranged between 3 and 4% and it was an independent entity associated with early mortality after 10 days. Ferritin was proposed as a diagnostic and surrogate biomarker. Concentrations >4,420 ng/ml were associated with diagnosis of MALS with 97.1% specificity and 98% negative predictive value. Increased ferritin was also associated with increased IL-6, IL-18, IFNγ, and sCD163 and by decreased IL-10/TNFα ratio. A drop of ferritin by 15% the first 48 h was a surrogate finding of favorable outcome. There are 10 on-going trials in adults with sHLH; two for the development of biomarkers and eight for management. Only one of them is focusing in sepsis. The acronym of the trial is PROVIDE (ClinicalTrials.gov NCT03332225) and it is a double-blind randomized clinical trial aiming to deliver to patients with septic shock treatment targeting their precise immune state. Patients diagnosed with MALS are receiving randomized treatment with placebo or the IL-1β blocker anakinra.
MeSH term(s)	Animals ; Biomarkers ; Clinical Trials as Topic ; Cytokines/genetics ; Cytokines/metabolism ; Diagnosis, Differential ; Disease Management ; Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/etiology ; Macrophage Activation Syndrome/diagnosis ; Macrophage Activation Syndrome/etiology ; Macrophage Activation Syndrome/mortality ; Macrophage Activation Syndrome/therapy ; Sepsis/diagnosis ; Sepsis/etiology ; Sepsis/therapy ; Signal Transduction ; Symptom Assessment
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2019-01-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00055
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Article: High levels of monocytic myeloid-derived suppressor cells are associated with favorable outcome in patients with pneumonia and sepsis with multi-organ failure.

Schrijver, Irene T / Karakike, Eleni / Théroude, Charlotte / Baumgartner, Pétra / Harari, Alexandre / Giamarellos-Bourboulis, Evangelos J / Calandra, Thierry / Roger, Thierry

Intensive care medicine experimental

2022 Volume 10, Issue 1, Page(s) 5

Abstract: Background: Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunosuppressive functions sub-classified into monocytic and polymorphonuclear MDSCs (M-MDSCs and PMN-MDSCs). Clinical studies reported increased levels of MDSCs that ... ...

Abstract	Background: Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunosuppressive functions sub-classified into monocytic and polymorphonuclear MDSCs (M-MDSCs and PMN-MDSCs). Clinical studies reported increased levels of MDSCs that were associated with poor outcome in sepsis patients. Since sepsis patients exhibit signs of inflammation and immunosuppression, MDSCs may provide benefit by dampening deleterious inflammation in some patients. To test this hypothesis, we measured MDSCs in critically ill sepsis patients with pneumonia and multi-organ dysfunctions and a high likelihood of death. Methods: This was a prospective multicenter observational cohort study performed in eight ICUs in Athens and Thessaloniki, Greece, enrolling critically ill patients with pneumonia and sepsis with multi-organ dysfunctions. A flow cytometry approach using blood collected at study inclusion in tubes containing lyophilized antibodies combined to unsupervised clustering was developed to quantify M-MDSCs and PMN-MDSCs. Results: Forty-eight patients were included, of whom 34 died within 90 days. At study inclusion, M-MDSCs and PMN-MDSCs were increased in sepsis patients when compared to healthy subjects (3.07% vs 0.96% and 22% vs 2.1% of leukocytes, respectively; p < 10 Conclusion: This is the first study to associate high levels of M-MDSCs with improved survival in sepsis patients.
Language	English
Publishing date	2022-02-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2740385-3
ISSN	2197-425X
ISSN	2197-425X
DOI	10.1186/s40635-022-00431-0
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Article: Infections in severe alcoholic hepatitis.

Karakike, Eleni / Moreno, Christophe / Gustot, Thierry

Annals of gastroenterology

2016 Volume 30, Issue 2, Page(s) 152–160

Abstract: Severe alcoholic hepatitis (sAH), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. Corticosteroid treatment remains the only ... ...

Abstract	Severe alcoholic hepatitis (sAH), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. Corticosteroid treatment remains the only therapeutic option that improves short-term survival. Infectious complications, occurring in approximately 50% of patients, are the main causes of death, even in patients who benefit from corticosteroids. Liver failure, recent alcohol consumption and immunosuppressive drugs contribute to this infectious risk. Although infection is a well-described feature of cirrhosis, little is known about the characteristics of infections in sAH. Infection is mainly of bacterial origin and frequently affects the respiratory tract. Pathogens classically observed in cirrhosis, such as gram-negative bacilli, are frequently involved, but opportunistic pathogens, such as fungi (
Language	English
Publishing date	2016-10-27
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	2032850-3
ISSN	1108-7471
ISSN	1108-7471
DOI	10.20524/aog.2016.0101
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Zs.A 2455: Show issues

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Article ; Online: Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis.

Karakike, Eleni / Giamarellos-Bourboulis, Evangelos J / Kyprianou, Miltiades / Fleischmann-Struzek, Carolin / Pletz, Mathias W / Netea, Mihai G / Reinhart, Konrad / Kyriazopoulou, Evdoxia

Critical care medicine

2021 Volume 49, Issue 12, Page(s) 2042–2057

Abstract: Objective: Coronavirus disease 2019 is a heterogeneous disease most frequently causing respiratory tract infection, which can induce respiratory failure and multiple organ dysfunction syndrome in its severe forms. The prevalence of coronavirus disease ... ...

Abstract	Objective: Coronavirus disease 2019 is a heterogeneous disease most frequently causing respiratory tract infection, which can induce respiratory failure and multiple organ dysfunction syndrome in its severe forms. The prevalence of coronavirus disease 2019-related sepsis is still unclear; we aimed to describe this in a systematic review. Data sources: MEDLINE (PubMed), Cochrane, and Google Scholar databases were searched based on a prespecified protocol (International Prospective Register for Systematic Reviews: CRD42020202018). Study selection: Studies reporting on patients with confirmed coronavirus disease 2019 diagnosed with sepsis according to sepsis-3 or according to the presence of infection-related organ dysfunctions necessitating organ support/replacement were included in the analysis. The primary end point was prevalence of coronavirus disease 2019-related sepsis among adults hospitalized in the ICU and the general ward. Among secondary end points were the need for ICU admission among patients initially hospitalized in the general ward and the prevalence of new onset of organ dysfunction in the ICU. Outcomes were expressed as proportions with respective 95% CI. Data extraction: Two reviewers independently screened and reviewed existing literature and assessed study quality with the Newcastle-Ottawa Scale and the Methodological index for nonrandomized studies. Data synthesis: Of 3,825 articles, 151 were analyzed, only five of which directly reported sepsis prevalence. Noting the high heterogeneity observed, coronavirus disease 2019-related sepsis prevalence was 77.9% (95% CI, 75.9-79.8; I2 = 91%; 57 studies) in the ICU, and 33.3% (95% CI, 30.3-36.4; I2 = 99%; 86 studies) in the general ward. ICU admission was required for 17.7% (95% CI, 12.9-23.6; I2 = 100%) of ward patients. Acute respiratory distress syndrome was the most common organ dysfunction in the ICU (87.5%; 95% CI, 83.3-90.7; I2 = 98%). Conclusions: The majority of coronavirus disease 2019 patients hospitalized in the ICU meet Sepsis-3 criteria and present infection-associated organ dysfunction. The medical and scientific community should be aware and systematically report viral sepsis for prognostic and treatment implications.
MeSH term(s)	COVID-19/complications ; Hospitalization/statistics & numerical data ; Humans ; Intensive Care Units/statistics & numerical data ; Multiple Organ Failure/etiology ; Patient Admission/statistics & numerical data ; SARS-CoV-2 ; Sepsis/etiology ; Sepsis/mortality ; Sepsis/virology ; Severity of Illness Index
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000005195
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Zs.A 1261: Show issues

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Article ; Online: The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort.

Karakike, Eleni / Kyriazopoulou, Evdoxia / Tsangaris, Iraklis / Routsi, Christina / Vincent, Jean-Louis / Giamarellos-Bourboulis, Evangelos J

Critical care (London, England)

2019 Volume 23, Issue 1, Page(s) 387

Abstract: Background: Since the Sepsis-3 criteria, change in Sequential Organ Failure Assessment (SOFA) score has become a key component of sepsis identification. Thus, it could be argued that reversal of this change (Δ: Methods: Data from two previously ... ...

Abstract	Background: Since the Sepsis-3 criteria, change in Sequential Organ Failure Assessment (SOFA) score has become a key component of sepsis identification. Thus, it could be argued that reversal of this change (Δ Methods: Data from two previously published randomized controlled trials were studied: the first reporting on patients with severe Gram-negative infections as a derivation cohort and the second reporting on patients with ventilator-associated pneumonia as a validation cohort. Only patients with sepsis according to the Sepsis-3 definition were included in this analysis. SOFA scores were calculated on days 1, 2, 3, 5, 7, 14, and 28. Results: We included 448 patients within the derivation cohort and 199 within the validation cohort. Mean SOFA scores on day 1 were 6.06 ± 4.07 and 7.84 ± 3.39, and 28 day mortality 22.8% and 29.6%, respectively. In the derivation cohort, the earliest time point where Δ Conclusions: Δ Trial registration: ClinicalTrials.gov numbers NCT01223690 and NCT00297674.
MeSH term(s)	Aged ; Area Under Curve ; Cohort Studies ; Female ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Odds Ratio ; Organ Dysfunction Scores ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis/mortality ; Statistics, Nonparametric
Keywords	covid19
Language	English
Publishing date	2019-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2051256-9
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-019-2665-5
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Article ; Online: IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19.

Renieris, Georgios / Karakike, Eleni / Gkavogianni, Theologia / Droggiti, Dionysia-Eirini / Stylianakis, Emmanouil / Andriopoulou, Theano / Spanou, Victoria-Marina / Kafousopoulos, Dionyssios / Netea, Mihai G / Eugen-Olsen, Jesper / Simard, John / Giamarellos-Bourboulis, Evangelos J

Journal of innate immunity

2022 Volume 14, Issue 6, Page(s) 643–656

Abstract: Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and ... ...

Abstract	Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.
MeSH term(s)	Humans ; Mice ; Animals ; COVID-19 ; Respiratory Insufficiency ; Receptors, Interleukin-1
Chemical Substances	Receptors, Interleukin-1
Language	English
Publishing date	2022-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2454158-8
ISSN	1662-8128 ; 1662-811X
ISSN (online)	1662-8128
ISSN	1662-811X
DOI	10.1159/000524560
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Article ; Online: Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

Karakike, Eleni / Scicluna, Brendon P / Roumpoutsou, Maria / Mitrou, Ioannis / Karampela, Niki / Karageorgos, Athanasios / Psaroulis, Konstantinos / Massa, Eleni / Pitsoulis, Achillefs / Chaloulis, Panagiotis / Pappa, Evanthia / Schrijver, Irene T / Frantzeskaki, Frantzeska / Lada, Malvina / Dauby, Nicolas / De Bels, David / Floros, Ioannis / Anisoglou, Souzana / Antoniadou, Eleni /

Patrani, Maria / Vlachogianni, Glykeria / Mouloudi, Eleni / Antoniadou, Anastasia / Grimaldi, David / Roger, Thierry / Wiersinga, W Joost / Tsangaris, Iraklis / Giamarellos-Bourboulis, Evangelos J

Critical care (London, England)

2022 Volume 26, Issue 1, Page(s) 183

Abstract: Background: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients ...

Abstract	Background: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. Methods: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Results: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Conclusions: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.
MeSH term(s)	Administration, Intravenous ; Clarithromycin/pharmacology ; Clarithromycin/therapeutic use ; Humans ; Multiple Organ Failure/complications ; Multiple Organ Failure/drug therapy ; Oxygen/therapeutic use ; Sepsis/complications
Chemical Substances	Clarithromycin (H1250JIK0A) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-06-18
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-022-04055-4
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Zs.A 5517: Show issues

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Article ; Online: Differential response induced by LPS and MPLA in immunocompetent and septic individuals.

Albert Vega, Chloé / Karakike, Eleni / Bartolo, François / Mouton, William / Cerrato, Elisabeth / Brengel-Pesce, Karen / Giamarellos-Bourboulis, Evangelos J / Mallet, François / Trouillet-Assant, Sophie

Clinical immunology (Orlando, Fla.)

2021 Volume 226, Page(s) 108714

Abstract: Lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA) induce, overall, similar transcriptional profiles in healthy individuals, although LPS has been shown to more potently induce pro-inflammatory cytokines. We explore herein whether MPLA could be ... ...

Abstract	Lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA) induce, overall, similar transcriptional profiles in healthy individuals, although LPS has been shown to more potently induce pro-inflammatory cytokines. We explore herein whether MPLA could be considered as a synthetic replacement of LPS in immune functional assays to study anergy of immune cells in septic patients. Ex vivo whole blood stimulation with MPLA revealed a lower induction of the TNFα secreted protein in 20 septic patients (SP) compared to 10 healthy volunteers (HV), in agreement with monocyte anergy. Principal component analysis of the 93-gene molecular response to MPLA and LPS stimulation found that the main variability was driven by stimulation in HV and by pathophysiology in SP. MPLA was a stronger inducer of the HLA family genes than LPS in both populations, arguing for divergent signalling pathways downstream of TLR-4. In addition, MPLA appeared to present a more informative stratification potential within the septic population.
MeSH term(s)	Aged ; Aged, 80 and over ; Cytokines/immunology ; Female ; Humans ; Immunocompromised Host/immunology ; Inflammation/immunology ; Lipid A/analogs & derivatives ; Lipid A/immunology ; Lipopolysaccharides/immunology ; Male ; Monocytes/immunology ; Prospective Studies ; Sepsis/immunology ; Signal Transduction/immunology ; Toll-Like Receptor 4/immunology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Cytokines ; Lipid A ; Lipopolysaccharides ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; monophosphoryl lipid A (MWC0ET1L2P)
Language	English
Publishing date	2021-03-16
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2021.108714
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Article ; Online: IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19

Georgios Renieris / Eleni Karakike / Theologia Gkavogianni / Dionysia-Eirini Droggiti / Emmanouil Stylianakis / Theano Andriopoulou / Victoria-Marina Spanou / Dionyssios Kafousopoulos / Mihai G. Netea / Jesper Eugen-Olsen / John Simard / Evangelos J. Giamarellos-Bourboulis

Journal of Innate Immunity, Pp 1-

2022 Volume 14

Abstract	Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.
Keywords	calprotectin ; tumor necrosis factor ; interleukin-6 ; interleukin-1 ; soluble urokinase plasminogen activator receptor ; acute respiratory distress syndrome ; severe respiratory failure ; coronavirus diseases 2019 ; Medicine ; R ; Internal medicine ; RC31-1245
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Karger Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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